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Patrick Shean-Young Lee, Haijing Sun, Nan Gao, Fushin X Yu; Role of MMP13 in Wound Healing in the Diabetic Mouse Cornea. Invest. Ophthalmol. Vis. Sci. 2017;58(8):158.
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Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases thought to regulate the process of wound repair. MMP-13 is one of three mammalian MMPs able to cleave fibrillar collagen, a key component of the extracellular matrix and basement membrane, a critical step in wound healing. This study sought to investigate the role of MMP-13 in the wound healing process and its role in the dysfunction observed with diabetic wound healing.
Corneas were wounded by debridement and allowed to heal in vivo. Epithelium was collected and assessed using qRT-PCR, western blotting, and immunohistochemistry. Fluorescein staining was used to assess wound size after debridement. Inhibitors and recombinant protein were subconjunctivally injected prior to epithelium-wounding and their effects on the rate of epithelial wound closure were determined.
Corneal epithelial expression of MMP-13 was found to be increased after wounding in normal B6 mice, as shown by real-time PCR, regular PCR, western blotting, and immunohistochemistry. This increase in expression was significantly attenuated in streptozotocin-induced diabetic B6 mice after wounding. MMP-13 inhibitor administered by subconjunctival siRNA injections in wounded mice resulted in a decrease in the rate of wound healing, reproducing the effects of delayed wound healing observed in diabetic corneas.
MMP-13 expressed in corneal epithelial cells plays a role in the corneal epithelial wound healing process. The hyperglycemia-suppressed expression of MMP-13 may be responsible in part for the delayed wound healing observed in diabetic neurotrophic keratopathy.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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